First clinical experience with intravenous recombinant human relaxin in compensated heart failure.

Relaxin is upregulated and plays a compensatory role in human heart failure. We therefore determined the safety of and dose response to human relaxin in stable patients with heart failure. Sixteen patients were treated with open-label intravenous relaxin in three sequential dose cohorts and monitored hemodynamically during the 24-h infusion and postinfusion periods. The safety demonstrated in group A (treatment for 8 h each with dosages equivalent to 10, 30, and 100 microg/kg/day) allowed escalation to group B (240, 480, and 960 microg/kg/day), and the highest safe dose, 960 microg/kg/day, was selected for a 24-h dosing in group C. Relaxin showed no relevant adverse effects and produced hemodynamic effects consistent with systemic vasodilation, i.e., trends toward increases in the cardiac index and decreases in pulmonary wedge pressure, without inducing hypotension. The first therapeutic use of relaxin in human heart failure demonstrated favorable hemodynamic effects and indicated that it may be of value in the treatment of this widespread disease.

Intravenous recombinant human relaxin in compensated heart failure: a safety, tolerability, and pharmacodynamic trial.

BACKGROUND: Relaxin is upregulated in human heart failure (HF). Animal and clinical data suggest beneficial hemodynamic and renal effects from vasodilation. We determined safety, tolerability, and pharmacodynamic effects of human Relaxin in stable HF. METHODS AND RESULTS: Sixteen patients were treated with open-label intravenous Relaxin in 3 dose-escalation cohorts and monitored hemodynamically for 24-hour infusion and postinfusion periods and followed until Day 30. The safety demonstrated in Group A (8-hour sequential infusions at dose levels of 10, then 30, and then 100 microg x kg x day equivalents) allowed escalation to Group B (240, 480, and 960 microg x kg x day). The highest safe dose, 960 microg x kg x day, was selected for a 24-hour infusion in Group C. Relaxin showed no adverse effects; produced hemodynamic effects consistent with vasodilation (ie, trends toward increases in cardiac index, decreases in pulmonary wedge pressure, and decreases in circulating NT-pro BNP without inducing hypotension; improved markers of renal function [creatinine, blood urea nitrogen]). The highest dose caused a transient elevation in creatinine and blood urea nitrogen at Day 9 that was without apparent clinical significance. CONCLUSIONS: Relaxin was safe and well-tolerated in patients with stable HF, and preliminary pharmacodynamic responses suggest it causes vasodilation. Further evaluation of the safety and efficacy of this drug in HF appears warranted.